An Elastomer with In Situ Generated Pure Zwitterionic Surfaces for Fibrosis-resistant Implants.

Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices.

Poly(Glutamic Acid-Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non-Human Primates.

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

Deficiency in SPOP-mediated ubiquitination and degradation of TIAM1 promotes gastric cancer progression.

It was well known that SPOP is highly mutated in various cancers especially the prostate cancer and SPOP mutation dramatically impaired its tumor suppressive function. However, the detailed role and underlying mechanisms of SPOP in regulating the growth of gastric cancer is not fully studied. Here, we found that Cullin3SPOP promoted the ubiquitination and degradation of TIAM1 protein in gastric cancer setting. Gastric cancer and prostate cancer derived SPOP mutation failed to suppress the proliferation, migration and invasion of gastric cancer cells partially due to the elevated level of TIAM1 protein. Notably, SPOP protein were negatively associated with TIAM1 protein in human gastric cancer tissue specimens. In conclusion, our results elucidate a molecular mechanism by which SPOP regulates the stability of TIAM1, and further demonstrate that SPOP inhibits the progression of gastric cancer by promoting the ubiquitination and degradation of TIAM1 protein.

Covalently grafted human serum albumin coating mitigates the foreign body response against silicone implants in mice.

Implantable biomaterials and biosensors are integral components of modern medical systems but often encounter hindrances due to the foreign body response (FBR). Herein, we report an albumin coating strategy aimed at addressing this challenge. Using a facile and scalable silane coupling strategy, human serum albumin (HSA) is covalently grafted to the surface of polydimethylsiloxane (PDMS) implants. This covalently grafted albumin coating remains stable and resistant to displacement by other proteins. Notably, the PDMS with covalently grafted HSA strongly resists the fibrotic capsule formation following a 180-day subcutaneous implantation in C57BL/6 mice. Furthermore, the albumin coating led to reduced recruitment of macrophages and triggered a mild immune activation pattern. Exploration of albumin coatings sourced from various mammalian species has shown that only HSA exhibited a promising anti-FBR effect. The albumin coating method reported here holds the potential to improve and extend the function of silicone-based implants by mitigating the host responses to subcutaneously implanted biomaterials.

Fibrous capsule-resistant, controllably degradable and functionalizable zwitterion-albumin hybrid hydrogels.

Foreign body response (FBR) represents an immune-mediated cascade reaction capable of inducing the rejection of foreign implants, thereby compromising their in vivo performance. Pure zwitterionic hydrogels have demonstrated the ability to resist long-term FBR, owing to their outstanding antifouling capabilities. However, achieving such a robust anti-FBR effect necessitates stringent requirements concerning the purity of zwitterionic materials, which constrains their broader functional applications. Herein, we present a biocompatible, controllably degradable, and functionalizable zwitterion-albumin hybrid hydrogel. The zwitterionic hydrogel crosslinked with serum albumin exhibits controllable degradation and excels in preventing the adsorption of various proteins and adhesion of cells and bacteria. Moreover, the hydrogel significantly alleviates the host's FBR compared with PEG hydrogels and particularly outperforms PEG-based cross-linker crosslinked zwitterionic hydrogels in reducing collagen encapsulation when subcutaneously implanted into mice. The zwitterion-albumin hybrid hydrogel shows potential as a functionalizable anti-FBR material in the context of implantable materials and biomedical devices.

MLKL deficiency alleviates neuroinflammation and motor deficits in the α-synuclein transgenic mouse model of Parkinson's disease.

Parkinson's disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) is involved in various diseases, including inflammatory bowel disease and neurodegenerative diseases; however, its precise role in PD remains unclear. Here, we investigated the neuroprotective role of MLKL inhibition or ablation against primary neuronal cells and human iPSC-derived midbrain organoids induced by toxic α-Synuclein preformed fibrils (PFFs). Using a mouse model (Tg-Mlkl-/-) generated by crossbreeding the SNCA A53T synuclein transgenic mice with MLKL knockout (KO)mice, we assessed the impact of MLKL deficiency on the progression of Parkinsonian traits. Our findings demonstrate that Tg-Mlkl-/- mice exhibited a significant improvement in motor symptoms and reduced phosphorylated α-synuclein expression compared to the classic A53T transgenic mice. Furthermore, MLKL deficiency alleviated tyrosine hydroxylase (TH)-positive neuron loss and attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes. Single-cell RNA-seq (scRNA-seq) analysis of the SN of Tg-Mlkl-/- mice revealed a unique cell type-specific transcriptome profile, including downregulated prostaglandin D synthase (PTGDS) expression, indicating reduced microglial cells and dampened neuron death. Thus, MLKL represents a critical therapeutic target for reducing neuroinflammation and preventing motor deficits in PD.

Hemoglobin as a prognostic marker for neurological outcomes in post-cardiac arrest patients: a meta-analysis.

The aim of this study was to investigate the relationship between serum level of hemoglobin and neurological outcomes following cardiac arrest. Relevant studies were identified by searching electronic databases including PubMed, Web of Science, Cochrane Library, and Embase from June 2012 through April 2023. Articles were rigorously reviewed for their study inclusion and exclusion criteria. Pooled effect date was determined using the standardized mean difference (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa Scale was used to evaluate study quality. Subgroup analyses were conducted to determine confounding factors affecting patient outcomes. Study heterogeneity, sensitivity, and publication bias were also determined.This meta-analysis included 11 studies involving 2519 patients. Our results suggest that high serum level of hemoglobin may improve neurological prognosis(SMD = 0.60, 95%CI = 0.49-0.71, I2 = 10.85). The findings of this study indicate that serum level of hemoglobin may be associated with better neurological prognosis, perhaps an appropriate increase in serum haemoglobin levels can improve the neurological prognosis of patients in cardiac arrest.

Harnessing the therapeutic potential of mesenchymal stem cell-derived exosomes in cardiac arrest: Current advances and future perspectives.

BACKGROUND: Cardiac arrest (CA), characterized by sudden onset and high mortality rates, is one of the leading causes of death globally, with a survival rate of approximately 6-24%. Studies suggest that the restoration of spontaneous circulation (ROSC) hardly improved the mortality rate and prognosis of patients diagnosed with CA, largely due to ischemia-reperfusion injury. MAIN BODY: Mesenchymal stem cells (MSCs) exhibit self-renewal and strong potential for multilineage differentiation. Their effects are largely mediated by extracellular vesicles (EVs). Exosomes are the most extensively studied subgroup of EVs. EVs mainly mediate intercellular communication by transferring vesicular proteins, lipids, nucleic acids, and other substances to regulate multiple processes, such as cytokine production, cell proliferation, apoptosis, and metabolism. Thus, exosomes exhibit significant potential for therapeutic application in wound repair, tissue reconstruction, inflammatory reaction, and ischemic diseases. CONCLUSION: Based on similar pathological mechanisms underlying post-cardiac arrest syndrome involving various tissues and organs in many diseases, the review summarizes the therapeutic effects of MSC-derived exosomes and explores the prospects for their application in the treatment of CA.

LncRNA CRNDE binds hnRNPA1 to facilitate carbon monoxide poisoning-induced delayed encephalopathy via inhibiting UCHL5-mediated SMO deubiquitination.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is one of the most common complications following carbon monoxide intoxication. Long noncoding RNAs (lncRNAs) exert critical functions in numerous neurological disorders. We intended to investigate the role of CRNDE in DEACMP. The DEACMP model in rats and the oxygen-glucose deprivation/reoxygenation (OGD/R) model in PC-12 cells were established. Brain and cell injuries were assessed with H&E staining, Nissl staining, TUNEL and CCK8 assays, respectively. Related proteins and RNAs were quantified with western blot and qRT-PCR. The N6-methyladenosine (m6A) level was determined using MeRIP-qPCR and immunofluorescence. Loss and gain function studies were performed to investigate the biological function of CRNDE. The potential mechanisms between each factor were explored using RNA immunoprecipitation, RNA-pull down and co-immunoprecipitation. CRNDE was increased in the hippocampal tissues of DEACMP rats and in OGD/R-treated PC-12 cells, which was positively correlated to m6A modification. Knockdown of CRNDE reduced cell damage and elevated UCHL5 and SMO expressions in OGD/R-treated PC-12 cells. hnRNPA1 was upregulated in DEACMP. In addition, inhibiting hnRNPA1 prevented apoptosis in PC-12 cells subjected to OGD/R. hnRNPA1 bound to CRNDE and remained in the nucleus, which inhibited UCHL5 expression through the formation of CRNDE-hnRNPA1-mRNA complex. UCHL5 could inhibit SMO ubiquitination and suppress PC-12 cell apoptosis during OGD/R. CRNDE silencing blocked brain injury in DEACMP, while knocking down UCHL5 reversed these effects. CRNDE interacted with hnRNPA1 to facilitate DEACMP via inhibition of UCHL5-mediated SMO deubiquitination. CRNDE might be a latent therapeutic target for treating DEACMP.

LncRNA CRNDE Deteriorates Delayed Encephalopathy After Acute Carbon Monoxide Poisoning to Inactivate AKT/GSK3ß/ß-catenin Pathway via miR-212-5p.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most serious sequel of acute CO poisoning, with structure or function injury of the brain. LncRNA colorectal neoplasia differentially expressed (CRNDE) aberrant expression was involved in nerve cell injury; however, the mechanism of CRNDE in DEACMP remains elusive. CO poisoning model of Sprague-Dawley rats was established. Neurological function was measured by Morris water maze (MWM) testing. Histopathological condition of brain and hippocampus tissues was observed by hematoxylin and eosin (H&E), Nissl, and TUNEL staining. Pro-inflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Oxidative damage and apoptosis markers were determined by related detection assays. Cell apoptosis were evaluated by flow cytometry analysis. Luciferase report and RNA immunoprecipitation (RIP) assays were employed to identify the binding relationship of CRNDE and miR-212-5p. CRNDE was significantly increased in CO poisoning animal model and oxygen-glucose deprivation (OGD) group, while that of miR-212-5p was decreased. CRNDE knockdown repressed the histopathological damage and apoptosis of brain and hippocampus tissues. Besides, CRNDE suppressed the AKT/GSK3ß/ß-catenin signaling pathway via targeting miR-212-5p. Furthermore, the protective effects of CRNDE silencing on brain tissue injury and apoptosis and AKT/GSK3ß/ß-catenin signaling pathway were reversed by inhibition of miR-212-5p in CO poisoning model. Collectively, CRNDE, serving as a sponge of miR-212-5p, aggravated the injury and apoptosis of brain and hippocampus tissues through regulating AKT/GSK3ß/ß-catenin signaling pathway under the CO-poisoning and OGD-treated model, suggesting a selected therapeutic target of DEACMP.

circXRCC5 foster gastric cancer growth and metastasis by the HNRNPC/circXRCC5/miR-655-3p/RREB1/UBA2 positive feedback loop.

Gastric cancer (GC) is one of the most common malignancies, leading to millions of deaths each year. Here, we investigated the molecular mechanisms of GC, with a focus on circXRCC5/miR-655-3p/RREB1/UBA2 axis. circXRCC5 was identified in 62 paired cancer specimens and adjacent normal tissues by genome-wide bioinformatics analysis and verified by qRT-PCR and Sanger sequencing. Knockdown or exogenous expression of circXRCC5 was performed to validate the functional significance of circXRCC5 using both in vitro and in vivo assays, including CCK-8, colony formation, EdU incorporation, transwell system, as well as animal experiments. RNA immunoprecipitation, biotinylated RNA pull-down, ChIP, and dual-luciferase assays were employed to validate the regulatory network of circXRCC5/miR-655-3p/RREB1/UBA2. Frequently elevated circXRCC5 in GC tissues and cell lines was associated with poor prognosis of GC patients. Functionally, circXRCC5 overexpression facilitated GC cell proliferation, migration, and invasion, as well as promoted tumor growth and metastasis in vivo. Mechanistically, circXRCC5 served as a sponge of miR-655-3p to induce upregulation of RREB1. RREB1 was identified as a transcriptional activator of UBA2, thus contributing to GC tumorigenesis. Moreover, RNA binding protein (RBP) HNRNPC was proved to interact with circXRCC5 to promote circXRCC5 biogenesis. Collectively, circXRCC5 facilitates GC progression through the HNRNPC/circXRCC5/miR-655-3p/RREB1/UBA2 axis, which might bring novel therapeutic strategies for GC treatment.

Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling.

OBJECTIVE: Sepsis-associated encephalopathy (SAE) is a severe and common complication of sepsis and can induce cognitive dysfunction and apoptosis of neurons and neuroinflammation. Emodin has been confirmed to have anti-inflammatory effects. Thus, we sought to investigate the role of Emodin in SAE. METHODS: The cecal ligation and puncture (CLP) method was used for the establishment of SAE in mice model. For treatment of Emodin, intraperitoneal injection of 20 mg/kg Emodin was performed before the surgery. The Morris water maze and open field tests were carried for measurement of cognitive dysfunction. Hematoxylin and eosin staining was for histological analysis of hippocampus. Cell apoptosis of hippocampus neurons was measured by TUNEL staining. Pro-inflammatory and anti-inflammatory cytokines in hippocampus tissue homogenate were evaluated by ELISA. BDNF/TrkB signaling-related proteins (TrkB, p-TrkB, and BDNF), autophagy-related proteins (LC3 II/I and Beclin-1), and apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were detected by Western blotting. RESULTS: Emodin significantly inhibited apoptosis and induced autophagy in hippocampal neurons of CLP-treated mice. In addition, Emodin significantly ameliorated CLP-induced cognitive dysfunction and pathological injury in mice. Meanwhile, Emodin notably inhibited CLP-induced inflammatory responses in mice via upregulation of BDNF/TrkB signaling, while the effect of Emodin was partially reversed in the presence of K252a (BDNF/TrkB signaling inhibitor). CONCLUSION: Emodin significantly inhibited the progression of SAE via mediation of BDNF/TrkB signaling. Thus, Emodin might serve as a new agent for SAE treatment.

SERPINE1 associated with remodeling of the tumor microenvironment in colon cancer progression: a novel therapeutic target.

BACKGROUND: The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. METHODS: In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. RESULTS: By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. CONCLUSION: We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.

The emerging role of miR-10 family in gastric cancer.

Evidence has demonstrated that miRNAs play an irreplaceable role in tumorigenesis and progression of a broad range of cancers, including gastric cancer. Among these miRNAs, miR-10a and miR-10b have been identified to critically participate in gastric carcinogenesis and malignant progression. In this review, we briefly describe the role of miR-10a and miR-10b in gastric cancer, especially in the regulation of cell proliferation, apoptosis, cell cycle, migration, invasion and metastasis, drug resistance, and cancer stem cells. Furthermore, we highlight several compounds that target the miR-10 family and exhibit antitumor activity in cancer cells. Moreover, we conclude that targeting the miR-10 family might be a promising approach for the treatment of gastric cancer.

LncRNA SNHG1 protects SH-SY5Y cells from hypoxic injury through miR-140-5p/Bcl-XL axis.

Background: Hypoxic brain injury is one of the major causes of neurodevelopmental impairment and cardiovascular disability. LncRNA SNHG1 works as a critical factor in hypoxic induced injury, however, the potential mechanism is still not known well.Methods: The expression level of small nucleolar RNA host gene 1 (SNHG1) and miR-140-5p was detected by qRT-PCR. The western blot assay was performed to measure the level of Bcl-XL and apoptosis-related proteins. The target relationship between lncRNA SNHG1 and miR-140-5p, as well as miR-140-5p and Bcl-XL was detected by dual luciferase reporter gene assay. Cell apoptosis was assessed using Annexin V/PI staining by flow cytometry. Cell viability was analyzed by MTT assay.Results: Oxygen glucose deprivation (OGD) treatment inhibited SNHG1 and Bcl-XL expression and enhanced miR-140-5p expression. OGD treatment-induced cell viability inhibition, cell apoptosis promotion were partially abrogated when SH-SY5Y cells were transfected with pcDNA3.1-SNHG1 or miR-140-5p inhibitor. Moreover, luciferase reporter assay revealed that lncRNA SNHG1 bound directly to miR-140-5p, and miR-140-5p directly targeted Bcl-XL. The protective effect of SNHG1 overexpressing on cell apoptosis induced by OGD was attenuated after transfected with miR-140-5p mimic or sh-Bcl-XL in SH-SY5Y cells.Conclusion: LncRNA SNHG1-modulated miR-140-5p inhibition regulates Bcl-XL expression, thereby reducing cell apoptosis and recovering cell viability of SH-SY5Y cells. The results in this study provide novel insight into the mechanism of SNHG1 mediated signaling pathway during hypoxic brain injury.

The significance of serum HMGB1 level in humans with acute paraquat poisoning.

High-mobility group box 1 (HMGB1) mediates acute lung injury in a mouse model of paraquat poisoning. However, published reports showing a clinically relevant association between HMGB1 and paraquat exposure are lacking. The objective of the present study was to investigate the potential role of serum HMGB1 level as a prognostic marker of mortality in patients with paraquat poisoning in a clinical setting. This retrospective observational cohort study included a convenience sample of 92 patients with acute paraquat poisoning admitted to the emergency room (ER) of The First Hospital of Jilin University between January 2014 and December 2016. Baseline serum HMGB1 levels and other laboratory parameters were measured on admission. Cumulative incidence of mortality during the first 30 days after admission was 50% (n = 46/92). Serum HMGB1 levels were higher in fatalities than survivors (P = 0.015), 30-day mortality increased with increasing baseline serum HMGB1 level (P < 0.001), and higher serum HMGB1 levels were associated with an increase in 30-day mortality on Kaplan-Meier analysis. Multivariate Cox regression analysis identified baseline serum HMGB1 levels, white blood cell count, and serum lactic acid levels as independent prognostic markers of 30-day mortality. These data suggest that serum HMGB1 levels measured on admission to the ER are an independent predictor of 30-day mortality in patients with acute paraquat poisoning.

A Randomized Multicenter Clinical Trial of RPH With the Simplified Milligan-Morgan Hemorrhoidectomy in the Treatment of Mixed Hemorrhoids.

PURPOSE: To explore the safety and efficacy of Ruiyun procedure for hemorrhoids (RPH) or RPH with the simplified Milligan-Morgan hemorrhoidectomy (sMMH) in the treatment of mixed hemorrhoids. METHODS: This is a randomized, controlled, balanced, multicenter study of 3000 patients with mixed hemorrhoids. The outcomes and postoperative complications were compared between 5 types of surgeries. RESULTS: The efficacy rate was the highest in patients who received RPH+sMMH and decreased in the following order: patients who received RPH alone, MMH alone, procedure for prolapse and hemorrhoids (PPH) alone, and PPH+sMMH ( P < .05). The operation time was the shortest in patients who received RPH alone and increased in the following order: patients who received RPH+sMMH, PPH alone, MMH alone, and PPH+sMMH ( P < .01). The duration of postoperative hospitalization stay was the shortest in patients who received RPH alone and increased in the following order: PPH alone, RPH+sMMH, PPH+sMMH, and MMH alone ( P < .01). The incidence of postoperative hemorrhage, uroschesis, anal fissure, crissum hematoma or thrombosis, and anorectal stenosis was significantly lower in patients who received RPH+sMMH than in patients who received the other 4 types of surgical treatments ( P < .05, P < .01). No significant differences in postoperative rectovaginal fistula and anal incontinence were observed between the 5 groups of patients. CONCLUSIONS: RPH with or without simplified MMH can reduce the incidence of postoperative complications and improve the curative efficacy in the treatment of patients with mixed hemorrhoids.

[Treatment of Mixed Hemorrhoids by RPH with the Simplified Milligan-Morgan Surgery: a Multi-center, Randomized, Controlled Clinical Trial].

Objective To observe the safety and efficacy of RPH with the simplified. Milligan-Mor- gan(M-M) surgery on mixed hemorrhoids. Methods Totally 1 200 patients with mixed hemorrhoid were assigned to the control group(600 cases) and the treatment group(600 cases) according to randomized, parallel controlled,multi-center trial design. Patients in the control group received PPH with the simplified M-M surgery, and patients in the treatment group received RPH with the simplified M-M surgery. Postop- erative complications, operation time,the postoperative hospitalization days and the efficacy were ob- served. Results Compared with the control group, the numbers of postoperation hemorrhage, postop- erative uroschesis, anal fissure and anorectal stenosis in treatment group were decreased(P <0. 01 , P < 0. 05), operation time and the postoperative hospitalization days were decreased (P <0. 01 , P <0. 05 ), the cure rate for 3 and 12 months after operation were increased (P <0. 01, P <0. 05). Conclusions RPH with the simplified M-M surgery could reduce the incidence of postoperative complications,improve the clinical cure rate and the curative effect in treatment of mixed hemorrhoids.